Some children have visual disturbances that occur in the absence of, or are out of proportion to, their objective ophthalmological findings. These symptoms reflect a wide range of processes that may be benign or may be a sign of neurological, systemic, or psychiatric disease. This chapter deals with the neuro-ophthalmologic detection of organic and psychogenic disorders that may manifest as transient or unexplained visual loss in childhood.

Summary

Migraine is a prevalent condition worldwide. It has far-reaching individual and societal economic impact. Almost all migraineurs (95%) take medications for headache relief and the majority use over-the-counter (OTC) medications. OTC drugs are readily accessible, affordable and effective. These medications are commonly used without the advice of a healthcare professional, hence the potential for negative health outcomes due to improper use. To avoid these problems and their potentially harmful consequences (e.g. toxicity, adverse effects), major efforts should be directed towards educating the public about migraine and its treatment, including the appropriate use of OTC medications.

Familial hemiplegie migraine (FHM) is an autosomal dominant subtype of migraine with attacks, associated with transient episodes of hemiparesis. One of the genes for FHM has been assigned to chromosome 19p13. Detailed analysis of critical recombinants from two different chromosome 19-linked FHM families, using new markers indicated a 6-cM candidate region on 19p13.1–p13.2 flanked by loci D19S394 and D19S226. Another paroxysmal neurological disorder, episodic ataxia type 2 (EA-2), has also been linked to the same chromosomal region. Most of the interval was completely covered by YAC and cosmid contigs; the physical map yielded approximately 3 Mb encompassing several genes including the protein kinase substrate 80K-H (PRKCSH) gene. Since PRKCSH is involved in neuronal signal transduction, it was considered to be an FHM candidate gene. The genomic structure of this gene was established and mutation analysis for all exon and flanking intron sequences was performed in FHM- and EA-2-affected individuals. Five polymorphisms were identified, including a trinucleotide repeat length variation in the coding sequence. However, no potential disease causing mutation was found and therefore the PRKCSH gene can be excluded for both FHM and EA-2.

Summary

The annual cost of managing migraine totals billions of US dollars. This retrospective economic analysis of a clinical trial comparing subcutaneous dihydroergotamine mesylate (DHE) with subcutaneous sumatriptan in the treatment of acute migraine is appropriate because, although each product has been shown to be efficacious, the acquisition cost of sumatriptan is over 3 times that of DHE. Total costs in each treatment group were calculated and applied independently to 11 clinical trial efficacy measures.

Three of the efficacy measures showed no statistically significant difference between treatment arms, leading to a decision to use the less expensive DHE. In 4 of the efficacy measures, DHE was the obvious choice because it is more efficacious and less expensive. For the final 4 efficacy measures, where sumatriptan is more efficacious and more expensive, incremental cost-efficacy ratios were calculated to determine the additional expenditure required to achieve outcomes associated with quick relief.

Depending on the efficacy variable chosen and the assumptions used in the model, the incremental cost-efficacy ratios ranged from $US4000 to $US6700 per year (1993 dollars) for each additional patient who is successfully treated with sumatriptan compared with DHE. Therefore, in a population of 100 migraineurs, an additional 13 to 22 patients would achieve these short term benefits of sumatriptan, although it would cost an additional $US88 395 annually, given the assumptions made. Because each product has unique advantages, we conclude that the more cost-efficacious product is dependent on the outcome of interest and the amount that the patient or provider is willing to pay to achieve that outcome.

Summary

Spreading Cortical Depression (SCD) is the hyper-excitation, followed by extreme suppression of spontaneous electrical activity in the cortex. This work models SCD propagation using current dipoles to represent excitable pyramidal cells. An area of cortex, either gyrus or sulcus, supporting SCD is represented by surface dipoles oriented perpendicular to the surface. Magnetic fields created by these individual surface dipoles are calculated using the Biot-Savart law. We have assumed a plane volume conductor to represent the sulcus to simplify the mathematical derivation. The sources included in cortical surface area of 10−4mm2 is represented by a signal dipole. The magnetic field arising from the entire excited area of the cortex is obtained by summing the fields due to these individual dipoles. The simulated waveforms suggest that the shapes, amplitudes, and durations of the SCD signals depend on the size of the active area of cortex involved in SCD, as well as the location and orientation of the detector. Using this dipole model, we are able to simulate the Large Amplitude Waves (LAWs) similar to those observed by Barkley et al. (1990) while measuring spontaneous activity from migraine headache patients using the assumption that these LAWs arise from propagation of SCD across a sulcus. The shape of the simulated LAW waveform is strongly influenced by the relationships between the detector location and orientation, the propagation direction of the SCD wave, and the orientation of the sulcus.

Ocular motor nerve palsies in children pose a different clinical paradigm than in adults and require a specialized knowledge base for proper evaluation and treatment. Children with acute ocular motor nerve palsies come to medical attention because of diplopia, abnormal head posture, ptosis, ocular misalignment, or systemic disease. Those with chronic ocular motor nerve palsies are often referred because of strabismic amblyopia.

Recent advances in neuroimaging have improved our understanding of intracranial diseases in children. An integrated understanding of these disease has also emerged from the proliferation of multidisciplinary clinics and programs combining expertise in pediatric neurology, neurosurgery, neuropathology, neuroradiology, neuro-oncology, and neuro-ophthalmology. Genetic defects are increasingly implicated in the pathogenesis of various intracranial disorders, and basic research is elucidating many of these diseases at the molecular level, Refinement in neurosurgical management will undoubtedly continue to play a significant role in the treatment of these disorders, but the future holdss promise as preventative measures are expected tc arise from molecular genetic research.

“Optic disc elevation” is a reason for neuro-ophthalmologic referral common in children. The nature of the underlying disorder can often be predicted from the wording of the referring physician’s telephone call. Bilateral optic disc elevation without visual loss in a child with headaches, nausea, and vomiting of several months duration creates a high index of suspicion for papilledema (i.e., swelling of the optic discs secondary to elevated intracranial pressure). Blurring of the nasal disc margins which is noted as an incidental finding in an otherwise healthy child is usually found to be pseudopapilledema (i.e., real or apparent elevation of the optic discs due to local structural factors, which simulates swelling of the discs). Optic disc swelling in the setting of acute visual loss usually signifies optic neuritis.

Nature (1996-12-12) 384: 560-564
, December 12, 1996

THE headaches that accompany certain intracranial pathologies (such as meningitis, subarachnoid haemorrhage and tumour) have been considered to result from mechanical or chemical stimulation of pain-sensitive structures of the intracranial meninges1,2. Although the recurrent headache of migraine is of unknown origin and is not accompanied by an identifiable pathology, it shares with intracranial headaches features that suggest an exaggerated intracranial mechanosensitivity (worsening of the pain by coughing, breath-holding or sudden head movement1,3). One possible basis for such symptoms would be a sensitization of meningeal afferents to mechanical stimuli. Previous studies of neuronal responses to meningeal stimulation have focused primarily on cells in the central portion of the trigeminal pathway, and have not investigated the possible occurrence of sensitization4–12. We have recorded the activity of primary afferent neurons in the rat trigeminal ganglion that innervate the dural venous sinuses. Chemical stimulation of their dural receptive fields with inflammatory mediators both directly excited the neurons and enhanced their mechanical sensitivity, such that they were strongly activated by mechanical stimuli that initially had evoked little or no response. These properties of meningeal afferents (chemosensitivity and sensitization) may contribute to the intracranial mechanical hypersensitivity that is characteristic of some types of clinically occurring headaches, and may also contribute to the throbbing pain of migraine.